Treatment Patterns in Patients with Chronic Myeloid Leukemia in Chronic Phase in US Clinical Practice, with a Focus on Tyrosine Kinase Inhibitor Therapy Discontinuation

Abstract

▪Introduction:The NCCN guidelines have recently been updated to include recommendations on tyrosine kinase inhibitor (TKI) therapy discontinuation for patients with chronic myeloid leukemia in chronic phase (CML-CP). A recent physician survey on TKI therapy discontinuation practice showed that before publication of the NCCN recommendations, conditions under which physicians would consider TKI therapy discontinuation differed from these recommendations and may have resulted in discontinuation where deep response was not achieved and disease not adequately monitored (Ritchie, ASCO 2017). This study further assessed TKI therapy treatment patterns, using real-world patient-level data, with a focus on TKI therapy discontinuation.Methods:Patient-level data were abstracted from charts and collected via an online questionnaire, which was completed by US oncologists/hematologists between June 6 and July 28, 2017. Data were collected for adult patients diagnosed with CML-CP who were initiated on a TKI as first-line therapy, not as part of an interventional clinical trial, between January 2006 and March 2014. Patient demographics, clinical and treatment characteristics, and treatment patterns with a focus on TKI therapy discontinuation were described. All statistical analyses were descriptive.Results:Data were abstracted on 732 patients with CML-CP by 123 physicians. Patients were on average 56 years old, 60% were male, and 8% had an ECOG ≥ 2. Most patients (447; 61%) received imatinib (403 [90% of 447] had 400 mg QD; 29 [6%] had 600 mg QD as the initial dose) as first line therapy, 180 (25%) received dasatinib (126 [70% of 180] had 100 mg QD; 43 [24%] had 50mg BID as the initial dose), and 105 (14%) received nilotinib (51 [49% of 105] had 300 mg BID; 41 [39%] had 400 mg QD as the initial dose).Over an average observation period of 4.8 years from first-line TKI initiation, 598 (82%) patients were observed to remain on first-line therapy without interruptions, 82 (11%) patients switched directly to another treatment for CML (main reasons included loss of molecular response [37% of 82]; failure to achieve satisfactory response/resistance [30%]; and adverse event [18%]), 29 (4%) patients interrupted the treatment and restarted the same treatment (main reasons included adverse events [34% of 29]; the patient no longer wanted to take the medication/patient's anxiety [28%]; and economic reason [14%]), and 23 (3%) patients discontinued all CML therapy. See Table 1.In total, TKI therapy was discontinued in 25 of the 732 patients (3.4%) after they achieved an adequate response, with the intention to remain free of CML pharmacological therapy until disease relapse. Among these 25 patients, the main reasons for discontinuation included: the patient achieved an adequate response (40% of 25), the patient no longer wanted to take the medication/patient's anxiety (20%), adverse events (20%), and pregnancy or planning to become pregnant (12%). Before discontinuation, 52% of these 25 patients achieved undetectable BCR-ABL response, 20% a decrease in BCR-ABL of ≥4.5 log, 20% a 4 log reduction, and 4% a 3 log reduction. A proportion of 20% (of 25) patients maintained the response for 3 years before discontinuation, 24% 2 years, 24% 1 year, and 20% 6 months. A proportion of 52% (of 25) of patients had been on TKI therapy for ≥3 years before discontinuation, 16% 2 years, 16% 1 year, and 16% <1 year. Among these 25 patients, 6 (24%) patients experienced withdrawal syndrome and 5 (20%) relapsed.Conclusion:In this real-world study of 732 patients who started first-line TKI therapy for CML-CP between 2006 and 2014, TKI therapy discontinuation was attempted for 3.4% of patients who achieved an adequate response with the intention to remain free of CML pharmacological therapy until disease relapse, mainly before the release of NCCN recommendations on TKI therapy discontinuation. The findings also suggest a more conservative TKI therapy discontinuation practice versus that previously reported in the physician survey. Further studies are warranted to understand whether this trend would change following the communication and increased awareness of the new TKI therapy discontinuation guidelines. [Display omitted] DisclosuresRitchie:Novartis: Consultancy, Other: Research funding to my institution, and travel, Speakers Bureau; Bristol-Myers Squibb: Other: Research funding to my institution; Astellas Pharma: Other: Research funding to my institution; NS Pharma: Other: Research funding to my institution; Incyte: Consultancy, Speakers Bureau; Celgene: Consultancy, Other: Travel, Speakers Bureau; Pfizer: Consultancy, Other: Research funding to my institution. Latremouille-Viau:Novartis: Other: Analysis Group, Inc. has received consulting fees from Novartis; Analysis Group, Inc.: Employment. Guerin:Analysis Group, Inc: Employment; AbbVie Inc.: Other: I am an employee of Analysis Group, which received consulting fees from AbbVie ; Novartis: Other: I am an employee of Analysis Group, which received consulting fees from Novartis. Pivneva:Analysis Group, Inc: Employment; Novartis: Other: Analysis Group, Inc. has received consulting fees from Novartis. Habucky:Novartis: Employment. Ndife:Novartis Pharmaceuticals Corporation: Employment. Joseph:Novartis Pharmaceuticals Corporation: Employment; Pfizer: Other: stock/stock options; Amgen: Other: stock/stock options; Express Scripts: Other: stock/stock options. Atallah:ADC Therapeutics: Research Funding.